Diseases of the eye are numerous and frequently difficult to treat effectively. For example, some areas of the eye are difficult to reach with systemic medications, while medications applied topically tend to be transient and require numerous and repeated applications. Surgical treatment of still other diseases is invasive and often problematic as well, with many patients ineligible for surgical treatment.
For example, intraocular diseases, such as age-related macular degeneration (ARMD) and choroidal neovascularization (CNV), are the leading cause of irreversible vision loss in the United States, and yet currently available treatments for subfoveal CNV, which comprise the majority of CNV cases, are associated with only marginal visual improvement and outcomes. As few as one quarter of patients with CNV associated with ARMD are laser eligible, and at least half of those treated experience recurrence of the disease with poor visual outcomes. Similarly, photodynamic therapy using verteporfin is only useful for the small minority of patients with vessels that are angiographically classified as “predominantly classic,” and even then the visual outcomes of such treatments are disappointing.
Pharmacologic therapy using local drug delivery or systemic drug delivery is also being investigated using drugs that are antiangiogenic. Such drugs include angiostatic steroids, metalloproteinase inhibitors and VEGF binding drugs. However, the problem common to all of these promising drugs is the transient nature of the therapeutic level requires frequent intravitreal injection.
Nonspecific uveitis is another devastating eye disease that affects millions of people in the world. Uveitis produces a wide spectrum of inflammation of most parts of the eye and chronic uveitis can be devastating in adults and children. Surgically implanted steroids have shown that high intraocular doses for sustained times are extremely beneficial to choronic uveitis patients, but this implant has surgically related side effects.
Intravitreal injection is being used in clinical trials of therapeutic agents, but pose a risk of infection that is estimated to be 0.5% per injection. Due to the short vitreous half-life of most small molecules after intravitreal injection, frequent injection is needed, which significantly increases the chance of intraocular infection.
Delivery of drugs into vitreous via liposomes or slow release crystalline lipid prodrugs extend the drug vitreous half-life, but traditional liposomes or self-assembling liposomes often decrease vitreous clarity when used, can not be easily customized to release drugs with different physicochemical properties, and do not “report” drug release information.
Extraocular diseases are also difficult to treat because, for example, eye drops applied topically require repeated and frequent doses.